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A comprehensive DNA methylation atlas for noncancer human tissue types

ABSTRACT: A comprehensive DNA methylation atlas for noncancer human tissue types

PROVIDER: PRJNA976234 | ENA |

REPOSITORIES: ENA

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A comprehensive DNA methylation atlas for noncancer human tissue types

Project description:Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Here we present one of the largest comprehensive and high-resolution methylation atlas based on Reduced Representative Bisulfite Sequencing (RRBS) data of 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively alidated the methylation signature atlas in independent methylation datasets, orthogonal epigenomic markers, and transcription regulatory elements. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA.

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DNA methylation atlas of normal human cell types

Project description:DNA methylation is a fundamental epigenetic mark that governs chromatin organization, cell identity, and gene expression. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell-type are >99.5% identical, demonstrating robustness of cell identity programs to genetic variation and environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny, and identifies methylation patterns retained since gastrulation. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hyper-methylated loci are rare and are enriched for CpG islands, polycomb targets, and CTCF binding sites, suggesting a novel role in shaping cell type-specific chromatin looping. The atlas provides an essential resource for interpretation of disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

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Project description:This experiment consists of expression profiles for proteins in human tissues based on immunohistochemistry tissue microarrays. The tissue and cell samples came from 144 normal individuals. Normal tissues are represented by samples from three individuals each (except for endometrium, skin, soft tissue and stomach which are represented by samples from six individuals each), one core per individual. <br> The data presented here is based on The Human Protein Atlas version 13 and Ensembl version 75.37. This entry represents a top level summary of the metadata only. For more information about the immunochemistry assays and how the tissue microarrays work for the assays, please visit the Human Protein Atlas website: http://www.proteinatlas.org/about/assays+annotation#ih

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